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Molecular biology of β-lactam acylases

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Abstract

β-Lactam acylases such as penicillin G acylases, penicillin V acylases and glutaryl 7-aminocephalosporanic acid acylases are used in the manufacture of 6-aminopenicillanic acid, 7-aminodesacetoxycephalosporanic acid and 7-aminocephalosporanic acid (7-ACA). Genetically-engineered strains producing 1050 U/g, 3200 U/g and 7000 to 10,000 U/I of penicillin G acylase, penicillin V acylase and glutaryl-7-ACA acylase, respectively, have been developed. The penicillin G acylase studied to date and the glutaryl-7-ACA acylase from Pseudomonas sp. share some common features: the active enzyme molecules are composed of two dissimilar subunits that are generated from respective precursor polypeptide; the proteolytic processing is a post-translational modification which is regulated by temperature; and the Ser residue at the N-terminus of the β-sub-unit (Ser290; penicillin G acylase numbering) is implicated as the active site residue. Protein engineering, to generate penicillin G acylase molecules and their precursors with altered sequences, and the structure-function correlation of the engineered molecules are discussed.

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Authors
  1. B. S. Deshpande
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  2. S. S. Ambedkar
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  3. V. K. Sudhakaran
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  4. J. G. Shewale
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The authors are with Research and Development, Hindustan Antibiotics Ltd, Pimpri, Pune 411 018, India;

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Deshpande, B.S., Ambedkar, S.S., Sudhakaran, V.K. et al. Molecular biology of β-lactam acylases. World Journal of Microbiology & Biotechnology 10, 129–138 (1994). https://doi.org/10.1007/BF00360873

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